Cytokine-mediated differential induction of hepatic activator protein-1 genes.
BACKGROUND
Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) increase the synthesis of hepatic acute-phase proteins; these effects appear mediated by activation of transcription factors. The purpose of this study was to determine the effects of TNF-alpha and IL-6 on expression of the jun family of activator protein-1 (AP-1) transcription factors with the human hepatoma cell line HepG2, a well-characterized model of the hepatic acute-phase response.


METHODS
HepG2 cells, treated with either TNF-alpha (100 ng/ml) or IL-6 (10 ng/ml), were extracted for RNA and protein (total and nuclear) and analyzed.


RESULTS
TNF-alpha increased c-jun and junD mRNA and c-Jun and JunD protein levels, as well as AP-1 binding activity. IL-6 increased c-jun mRNA, c-Jun protein, and AP-1 binding activity but did not affect either junD or junB expression.


CONCLUSIONS
TNF-alpha and IL-6 induce a differential pattern of AP-1 expression in HepG2 cells; TNF-alpha increases both c-Jun and JunD, whereas IL-6 stimulates only c-Jun. Neither TNF-alpha nor IL-6 stimulates JunB. Multiple cytokines, released during stress, may act in concert to stimulate the AP-1 proteins, which ultimately culminate in the downstream synthesis of a variety of acute-phase proteins.
Wang
S
S
Department of Surgery, University of Texas Medical Branch, Galveston, 77555-0533, USA.
Evers
B M
BM
D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D015850:Interleukin-6; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha